Our recent studies have concerned the localization and function of calcium ions at the cell surface, topics that lie at the basis of many biological phenomena and that constitute one of the central problems in membrane biology. An understanding of the role of calcium will both require and enhance comprehension of various aspects of cellular calcium movement and regulation, and should have profound medical implications. Specific questions that interest us are the interaction of calcium with components of the cell membrane (lipids, carbohydrates, proteins, ATPases), the mechanism of calcium transport across epithelia, cellular aspects of calcification, and intracellular calcium homeostasis. These are complex and over-lapping problems requiring multi-diciplinary approaches for their solution. Although this is a rather vast topic for a research proposal, we have singled out several specific projects for further study. Our approach takes advantage of recent advances in the cellular localization of calcium ions. It has been found that under appropriate conditions of fixation and processing calcium ions can be retained within tissues and are sufficiently electron-opaque to be visualized in the electron microscope. New techniques of microprobe analysis, including use of frozen unfixed material, when correlated with physiological and morphological studies, should make possible significant advances in diverse aspects of the biology of calcium ions. While we may ultimately wish to obtain the apparatus for biological microprobe analysis, the microprobe aspects of these studies can be done in collaboration with other laboratories.